Acquired Immune Deficiency Syndrome (AIDS) has become a significant public health threat in recent years. A major breakthrough in AIDS research came in 1983-1984 when two groups independently isolated and identified a virus believed to be the causative agent of AIDS. The AIDS virus has been described by several names. It has been known as lymphadenopathy-associated virus (LAV), AIDS-related virus (ARV) and human immunodeficiency virus (HIV). Within the last few years, scientists have discovered that there are at least two distinct viruses, HIV-1 and HIV-2. HIV-1 is the virus originally isolated in 1983 (Ann. Virol. Inst. Pasteur, 135E:119-134 [1986]); HIV-2 was isolated by researchers in 1986 (see Nature, 326:662 [1987]). As used herein, HIV refers to these viruses generically.
A distinguishing feature of HIV is its selective cytotoxicity for helper T lymphocytes. The virus also infects monocytes/macrophages, B lymphocytes and neural cells. Severe and diverse aberrations of the immune system significantly reduce the host defense against various opportunistic infections, ultimately resulting in host death.
There are a number of proteins secreted by human cells that can regulate the human immune system. These secreted proteins with regulatory activities generally are classified as interleukins or cytokines. The United States Food and Drug Administration (FDA) has approved the use of some of the interleukins/cytokines in clinical trials for the treatment of AIDS. Those approved for clinical trials include interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-.alpha.), interferon-alpha (INF-.alpha.), interferon-beta (INF-.beta.), interferon-gamma (INF-.gamma.) and colony stimulating factor for granulocytes and macrophages (GM-CSF). Only the interferons have been shown to possess anti-viral activities before the initiation of the clinical trials. The high doses of interferon required in treatment often give undesirable short-term side effects that precipitate the withdrawal of the interferon treatment. IL-2 has shown no anti-HIV activity, and data available thus far suggest that IL-2 has no significant impact on the reconstitution of CD4-positive helper T cell populations in AIDS patients. Recent reports also have shown that TNF-.alpha.and GM-CSF can activate latent HIV in cells maintained in tissue culture. Thus, it is questionable if these agents can be used long-term to treat AIDS patients. There thus remains an urgent need for methods of inactivating the AIDS virus and for the treatment of AIDS.
It therefore is an object of the present invention to provide a novel protein having potent anti-HIV activity. It is a further object of the invention to provide a protein which can substantially inhibit the replication of HIV in HIV-infected cells. Other objects of the invention will become apparent from the following description.